Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0021051 (immunodeficiency)
 71,517 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

NPT 15392 (Erythro-9 (2-hydroxy-3 nonyl) hypoxanthine), a novel heterocyclic immunomodulatory compound, was analyzed over a broad concentration range on a variety of human blood leukocyte functions in vitro. NPT 15392 augmented mitogen-induced lymphocyte transformation in a variable fashion; lymphocytes from 9 of 24 individuals showed significant stimulation with phytohemagglutinin at 0.01 microgram/ml of NPT 15392, and 3 of 14 and 3 of 3 showed similar augmentation with concanavalin A and pokeweed mitogen, respectively. NPT 15392 above 10 microgram/ml inhibited mitogen responses and did not itself stimulate cell division. NPT 15392 also augmented responses of lymphocytes to antigenic stimulation with Candida and Staphylococcus antigens, purified protein derivative, and allogeneic cells in a variable manner. When observed, stimulation occurred at 0.01-1 microgram/ml of NPT 15392 for Candida and Staph. and at 0.01 microgram/ml with PPD and allogeneic cells. NPT 15392 (0.01-1 microgram/ml) consistently induced suppressor cell function alone and in combination with concanavalin A. This effect is apparently mediated by T lymphocytes since suppression was not mediated by interferon, prostaglandin or histamine. In addition, NPT 15392 (0.01-10 microgram/ml) significantly augmented "active" T cell rosettes. NPT 15392 over a broad concentration range and in the presence and absence of interferon did not stimulate natural killer cell activity or antibody-dependent cellular cytotoxicity. The data indicate that NPT 15392 is a modulator of such T lymphocyte functions as proliferative response to antigen and mitogen, suppressor activity and receptor display. Such activities imply potential therapeutic use in immunodeficiency related to defects of the thymus and thymus-derived lymphocytes.
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PMID:Effects of NPT 15392 in vitro on human leukocyte functions. 617 91

Enzyme inhibitors used to simulate the inherited immunodeficiency diseases, adenosine deaminase (ADA) and purine nucleoside phosphorylase (PNP) deficiency, have been assessed in cultured human lymphocytes. Only 2'-deoxycoformycin (dCF) completely inhibited ADA in T and B cells at concentrations in excess of 5 microM. Erythro-9-(2-hydroxy-3-nonyl) adenine (EHNA) and 8-amino guanosine (8-NH2GR) did not inhibit ADA or PNP completely at any concentration. Detailed metabolic experiments comparing viability and deoxynucleotide accumulation showed that B cell lines of malignant origin also accumulated high levels of dATP from 2'-deoxyadenosine (dAR), and dGTP from 2'-deoxyguanosine (dGR) as effectively as T cells--even without inhibitors, however, dAR reduced cell viability only when ADA was inhibited by dCF, whilst dGR was equally toxic with or without inhibitor, even to a line which accumulated no dGTP. These experiments indicate that cultured lymphocytes, using either EHNA or 8-NH2GR as enzyme inhibitor, are not valid models of the toxicity to the immune system in inherited ADA or PNP deficiency. They demonstrate that the ability to accumulate high levels of dATP or dGTP is not exclusive to T cells and that the in vitro toxicity of dAR or dGR could relate to the use of excess substrate and/or accumulation in different nucleotide, not deoxynucleotide pools.
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PMID:B cells as well as T cells form deoxynucleotides from either deoxyadenosine or deoxyguanosine. 642 86